Intravenous drug abusers represent a rapidly growing segment of new HIV infections and many initiatives are aimed at reducing the transmission of disease in this high risk group. One important approach is the enrollment and maintenance of opioid addicted persons in methadone treatment programs to help reduce risk-taking behavior. Antiretroviral therapy for the treatment of HIV infection is well established and the importance of early intervention is well founded. Antiretroviral agents prolong survival and diminish the rate of opportunistic infections, and may help reduce HIV-related dementia and neurodevelopmental abnormalities in children. However, currently available agents have had limited success, especially when prescribed alone. Greater success has been achieved with combinations of different antiretroviral agents. Combination therapies, including administration of zidovudine (AZT) and lamivudine (3TC), have resulted in increases in CD4+ counts and decreases in viral load over a 24 to 48 week period. Maintenance of effective methadone plasma concentrations is critical to the success of opioid replacement therapy and the reduction of high risk behavior including sharing of needles and unprotected intercourse. To date, there is no information on the effect of AZT, 3TC, and methadone combination therapy on any of the drugs' pharmacokinetic parameters. This information is essential for the successful application of both initiatives to reduce the morbidity and mortality of HIV infections in opioid addicted individuals. Physicians require this knowledge for designing effective dosing regimens and to reduce potential drug toxicities. In this study, the pharmacokinetics of methadone alone and in combination with AZT, and 3TC will be characterized in HIV positive subjects enrolled in a methadone maintenance program. Individuals will be stabilized on methadone in an outpatient program for approximately two weeks to reach steady state drug concentration. Subjects will be admitted to the clinical ward of the Addiction Research Center for approximately two weeks while receiving methadone and the combination antiretroviral treatment or placebo medication. Two additional weeks will follow as an outpatient in the methadone treatment program without antiretroviral drugs. Subjects will again be admitted for two more weeks with methadone and either active or placebo antiretroviral therapy, and finally, an opioid detoxification program will be administered. Frequent monitoring of plasma AZT, 3TC, methadone and metabolites, urine toxicology screens, and behavioral measures will occur. Surrogate markers, CD4+ counts and viral load, will be used to define successful therapeutic outcomes. This study is the first to address this important question and should provide information which will hopefully improve the treatment of opioid addicts with AIDS.